Pharmaceuticals can be developed from lead compounds that are identified through a random screening process directed towards a target, such as a receptor. Large scale screening approaches can be complicated by a number of factors. First, many assays are laborious or expensive to perform. Assays may involve experimental animals, cell lines or tissue cultures that are difficult or expensive to acquire or maintain. They may require the use of radioactive materials, and thus pose safety and disposal problems. These considerations often place practical limitations on the number of compounds that reasonably can be screened. Thus, those employing random screening methods are frequently forced to choose novel chemical compounds based on some prior knowledge suggesting the compounds are likely to be effective. This strategy limits the range of compounds tested, and many useful drugs may be overlooked.
Second, the specificity of many biochemical assays may overlook a wide variety of useful chemical compounds because the interactions between the ligand and the receptor protein are outside the scope of the assay. For example, many proteins have multiple functions, whereas most assays are capable of monitoring only one such activity. With such a specific assay, many potential pharmaceuticals are overlooked. Finally, in most existing biochemical screening approaches to drug discovery, the activity of the target protein must be defined. This requires that the system in question be well-characterized before screening can begin. Many new proteins are now identifiable through their DNA sequences. However, the specific functions of a protein encoded by a newly identified gene are usually not revealed by analysis of its DNA sequence. Consequently, biochemical screening for therapeutic drugs directed against many target proteins must await detailed biochemical characterization, a process which generally requires extensive research.